Xylene

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to fish, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

The target lipid model (TLM) is a framework that relates toxicity to the physicochemical properties of a nonpolar organic constituent. It is a well documented and peer reviewed model that is widely used across the petrochemicals industry. This substance fits within the criteria of the model and there are no reservations about the validity of the model runs. It is expected that this data is reliable with restrictions.

Qualifier:

no guideline required

Principles of method if other than guideline:

The endpoint calculated is the LL50, EL50, and NOELR -
The narcosis TLM was developed to predict the toxicity of chemicals to aquatic organisms that act via narcosis. It is based on the hypothesis that target lipid is the site of toxic action within the organism, that octanol is the appropriate surrogate, and that target lipid has the same physical–chemical properties in all organisms.
The approach describes:
• The theory and how to predict the acute toxicity to these organisms;
• Development of an Acute to Chronic ratio [ACR] for only hydrocarbons and for 29 data points.

The logkow used for calculation:
m- xylene= 3.20

Specific details on test material used for the study:

N/A

Details on sampling:

N/A

Details on test solutions:

N/A

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

N/A

Post exposure observation period:

N/A

Hardness:

N/A

Test temperature:

N/A

pH:

N/A

Dissolved oxygen:

N/A

Salinity:

N/A

Conductivity:

N/A

Nominal and measured concentrations:

N/A

Details on test conditions:

N/A

Key result

Duration:

21 d

Dose descriptor:

NOELR

Effect conc.:

0.894 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

not specified

Remarks on result:

ChV (chronic value, QSAR)

Details on results:

N/A

Results with reference substance (positive control):

N/A

N/A

Conclusions:

The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 0.894 mg/L. The target substance is a hydrocarbon acting via baseline toxicity, and falls within the parametric, structural and mechanistic domain of the model.

Executive summary:

The long-term aquatic toxicity to this substance was estimated using the Target Lipid Model based on methodologies described by McGrath et al. (2004, 2015). The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 0.894 mg/L.

Reference 2

Endpoint:

long-term toxicity to fish, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

The Target Lipid Model (TLM) is a framework that relates toxicity to the physicochemical properties of a nonpolar organic constituent. It is a well documented and peer reviewed model that is widely used across the petrochemicals industry. This substance fits within the criteria of the model and there are no reservations about the validity of the model runs. It is expected that this data is reliable with restrictions.

Qualifier:

no guideline required

Principles of method if other than guideline:

The endpoint calculated is the LL50, EL50, and NOELR -
The narcosis TLM was developed to predict the toxicity of chemicals to aquatic organisms that act via narcosis. It is based on the hypothesis that target lipid is the site of toxic action within the organism, that octanol is the appropriate surrogate, and that target lipid has the same physical–chemical properties in all organisms.
The approach describes:
• The theory and how to predict the acute toxicity to these organisms;
• Development of an Acute to Chronic ratio [ACR] for only hydrocarbons and for 29 data points.

The logkow used for calculation:
o-xylene= 3.12

Specific details on test material used for the study:

N/A

Details on sampling:

N/A

Details on test solutions:

N/A

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

N/A

Post exposure observation period:

N/A

Hardness:

N/A

Test temperature:

N/A

pH:

N/A

Dissolved oxygen:

N/A

Salinity:

N/A

Conductivity:

N/A

Nominal and measured concentrations:

N/A

Details on test conditions:

N/A

Key result

Duration:

21 d

Dose descriptor:

NOELR

Effect conc.:

1.063 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

not specified

Remarks on result:

ChV (chronic value, QSAR)

Details on results:

N/A

Results with reference substance (positive control):

N/A

Reported statistics and error estimates:

N/A

N/A

Conclusions:

The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 1.063 mg/L. The target substance is a hydrocarbon acting via baseline toxicity, and falls within the parametric, structural and mechanistic domain of the model.

Executive summary:

The long-term aquatic toxicity to this substance was estimated using the Target Lipid Model based on methodologies described by McGrath et al. (2004, 2015). The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 1.063 mg/L.

Reference 3

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016 to 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Purity: 99.8%
Batch No.: SHBG3928V

Analytical monitoring:

yes

Details on sampling:

Samples of test media including the control group were taken from alternating test replicates on days -1, 0 and weekly thereafter until the end of exposure.

Vehicle:

yes

Remarks:

Methanol

Details on test solutions:

Nominal test item concentrations of 2.50 - 5.00 - 10.0 mg/L (factor: 2.0), corresponding to arithmetic mean measured test item concentrations of 0.714 – 1.29 – 2.79 mg/L. Due to the low solubility of the test item in water, methanol was used as solvent with a loading of 0.10 mL/L dilution water. The stock solutions were prepared in methanol.

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

All fish used in the test were reared at Noack Laboratorien GmbH from a single brood stock (supplier: Umweltbundesamt, Schichauweg 58, D-12307 Berlin, Germany).
A breeding stock of unexposed, mature zebrafish with an age of 7 months was used for the egg production. Fish were free of macroscopically discernable symptoms of infection and disease. Spawners were maintained in aquaria with a loading capacity of a minimum of 1 L water per fish.
Fertilized eggs with more than 2 cells were placed directly in the test vessels. 20 eggs were introduced per replicate (corresponding to 80 eggs per treatment group). Eggs were less than 24 h old at experiment start.

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

35 d

Remarks on exposure duration:

30 days post hatch

Hardness:

Range: 49 – 72 mg CaCO3/L.
Arithmetic mean: 60 mg CaCO3/L in control and 63 mg CaCO3/L in the 2.79 mg/L treatment.

Test temperature:

25.6 – 26.7 °C

pH:

7.52 – 8.15

Dissolved oxygen:

Dissolved oxygen saturation was between 71 and 100 % of the air saturation value

Salinity:

N/A

Conductivity:

N/A

Nominal and measured concentrations:

Nominal concentrations: 2.5, 5.0, 10.0 mg/L
Arithmetic mean measured concentrations: 0.714 – 1.29 – 2.79 mg/L

Details on test conditions:

A test was conducted under flow-through conditions. Spawners were maintained in aquaria with a loading capacity of a minimum of 1 L water per fish. Temperature: 25 ± 2°C, Dissolved oxygen concentration > 60 % of air saturation value, pH value: 6 – 8.5, Photoperiod: 16 h light / 8 h dark cycle (2 transition periods, 30 minutes each), Diffuse light (7 – 750 lux on water surface), Food: Artemia salina nauplii, 48 hours old, ad libitum ; Daphnia magna, juvenile and adult daphnids, ad libitum; dry food sera vipan SERA, ad libitum.

TEST SYSTEM
- Test vessel: Glass aquaria provided with mesh (inert nylon fabric) coated fittings allowing flow-through of test media (dimensions: 22/22/18 cm) covered by glass lids
- Size of vessel: 8.7 L
- Material, size, headspace, fill volume: The volume of the test media was approximately 7.5 L
- Aeration: No additional aeration of the test vessels was provided. The dilution water supply tank was aerated.
- Renewal rate of test solution (frequency/flow rate): The mean flow rate through the mixing chambers of all test item and control groups was 8.13 ± 0.269 L/h and the individual values ranged from 7.68 to 9.12 L/h. The mean flow rates through the test aquaria were 1.86 ± 0.083 L/h and the individual values ranged from 1.71 to 2.04 L/h.
- No. of organisms per vessel: 20
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4
- Biomass loading rate: A loading rate not exceeding 0.5 g/L wet weight fish per 24 hours and not exceeding 5 g/L of solution at any time was maintained.

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Filtered tap water

EFFECT PARAMETERS MEASURED (with observation intervals if applicable): hatchability, time to hatch, fry growth (expressed as length and fresh weight), morphological and behavioral effects, post-hatch survival and overall survival (mortality).

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 2
- Justification for using less concentrations than requested by guideline: An extended limit test with 3 concentrations was chosen based on the results of a preliminary test.

RANGE-FINDING STUDY
- Test concentrations:
1st test (flow-through conditions with limited headspace, methanol as solvent): 0.25, 1.00 and 2.00 mg/L
2nd test (flow-through conditions with limited headspace, methanol as solvent): 5.00 and 10.0 mg/L
3rd test (static conditions with slow agitation, various headspace conditions and with /without methanol as solvent): 5 mg/L
- Results used to determine the conditions for the definitive study: No effects were observed in a preliminary test up to 4 days post-hatch.

Reference substance (positive control):

no

Key result

Duration:

35 d

Dose descriptor:

NOEC

Effect conc.:

0.714 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

other: Post hatch survival and overall survival

Duration:

35 d

Dose descriptor:

LOEC

Effect conc.:

1.29 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

other: Post hatch survival and overall survival

Details on results:

Hatchability and hatching time: NOEC >= 2.79 mg/L, LOEC > 2.79 mg/L
Fry growth (expressed as length and weight): NOEC 1.29 mg/L, LOEC 2.79 mg/L
Post hatch survival and overall survival (mortality): NOEC 0.714 mg/L, LOEC 1.29 mg/L

Validity criteria
Dissolved oxygen saturation was between 71 and 100 % of the air saturation value (required: > 60 %).
Water temperature did not differ by more than ± 1.5°C between test vessels or between successive days at any time during the test and was in the recommended range for the test species (i.e. 26°C ± 1.5°C): 26.3 ± 0.3°C.
Hatching success was 96 % in the control group and 99 % in the solvent control group (required: ≥ 70 %).
Post-hatch success was 75 % in the control group and 75 % in the solvent control group (required: ≥ 75 %).
Control analysis: the measured concentrations of the test item in the test solution were in the range of 15 to 62 % of the nominal values. Measured concentrations of the stock solutions were in the range of 97 to 100 % of the nominal values. All effect values were based on the arithmetical mean measured concentrations of p-Xylene.

Reported statistics and error estimates:

The post hatch survival data of study day 35 (PHD 30) were arcsine transformed prior to statistical analysis. The Williams multiple sequential t-test procedure (alpha = 0.05) was performed. Statistically significant differences were found for the arithmetical mean measured test item concentrations of 1.29 and 2.79 mg/L. The NOEC and the LOEC (arithmetical mean measured concentrations) for this endpoint were determined to be 0.714 and 1.29 mg/L, respectively.

Table 1:      Post-Hatch Survival on Study Day35 (PHD 30)of the Control, Solvent Control and the Arithmetic Mean Measured Test Item Concentrations of 0.714, 1.29 and 2.79 mg/L

Arithmetic mean measured test item conc. [mg/L]	Rep.	Cumulative hatched larvae n/20	Vital larvae on study day 35 (PHD 30) n/20	Post-hatch survival [%]	Post-hatch mortality [%]
Control	1	19	16	84	16
	2	19	13	68	32
	3	19	14	74	26
	4	20	15	75	25
	Mean	19.3	14.5	75	25
Solvent control	1	20	16	80	20
	2	20	12	60	40
	3	20	15	75	25
	4	19	16	84	16
	Mean	19.8	14.8	75	25
0.714	1	20	13	65	35
	2	20	13	65	35
	3	18	13	72	28
	4	20	10	50	50
	Mean	19.5	12.3	63 (-)	36
1.29	1	19	5	26	74
	2	20	8	40	60
	3	20	9	45	55
	4	18	0	0	100
	Mean	19.3	5.5	28 (+)	72
2.79	1	20	8	40	60
	2	19	6	32	68
	3	17	4	24	76
	4	19	2	11	89
	Mean	18.8	5.0	27 (+)	73

(-)  = No statistically significant difference from control groups

(+)  = Statistically significant difference from control groups  

Table 2: Cumulative Survival and Mortality on Study Day 35 (PHD 30) of the Control, Solvent Control and the Arithmetic Mean Measured Test Item Concentrations of 0.714, 1.29 and 2.79 mg/L 

Arithmetic mean measured test item conc. [mg/L]	Rep.	Vital larvae on study day 35 (PHD 30) n/20	Cumulative survival [%]	Mortality [%]
Control	1	16	80	20
	2	13	65	35
	3	14	70	30
	4	15	75	25
	Mean	14.5	73	27
Solvent control	1	16	80	20
	2	12	60	40
	3	15	75	25
	4	16	80	20
	Mean	14.8	74	26
0.714	1	13	65	35
	2	13	65	35
	3	13	65	35
	4	10	50	50
	Mean	12.3	61 (-)	39
1.29	1	5	25	75
	2	8	40	60
	3	9	45	55
	4	0	0	100
	Mean	5.5	28 (+)	72
2.79	1	8	40	60
	2	6	30	70
	3	4	20	80
	4	2	10	90
	Mean	5.0	25 (+)	75

(-)  = No statistically significant difference from control groups

(+)  = Statistically significant difference from control groups  

Validity criteria fulfilled:

yes

Conclusions:

The NOEC and LOEC of p-xylene to the early life stage of fish were determined to be 0.714 and 1.29 mg/L, respectively, based on post-hatch and overall survival.

Executive summary:

The effects of p-xylene to the early-life stage of fish (Danio rerio / Zebrafish) were determined according to OECD Guideline 210. An extended limit test was conducted under flow-through conditions with the nominal test item concentrations of 2.50 - 5.00 - 10.0 mg/L, corresponding to arithmetic mean measured test item concentration of 0.714 – 1.29 – 2.79 mg/L. Based on mean measured concentrations, NOEC and LOEC values had been determined for the relevant biological parameters. Whereas hatchability was not negatively influenced and the NOEC for this parameter had been determined as >= 2.79 mg/L, fry growth parameters (length /weight) demonstrated a NOEC of 1.29 mg/L (LOEC = 2.79mg/L). Post-hatch and overall survival as determined on experimental day 35 (day 30 post hatch) were the most sensitive endpoints with a NOEC value of 0.714 mg/L, and corresponding of LOEC of 1.29 mg/L.

Reference 4

Endpoint:

long-term toxicity to fish, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

The Target Lipid Model (TLM) is a framework that relates toxicity to the physicochemical properties of a nonpolar organic constituent. It is a well documented and peer reviewed model that is widely used across the petrochemicals industry. This substance fits within the criteria of the model and there are no reservations about the validity of the model runs. It is expected that this data is reliable with restrictions.

Qualifier:

no guideline required

Principles of method if other than guideline:

The endpoint calculated is the LL50, EL50, and NOELR -
The narcosis TLM was developed to predict the toxicity of chemicals to aquatic organisms that act via narcosis. It is based on the hypothesis that target lipid is the site of toxic action within the organism, that octanol is the appropriate surrogate, and that target lipid has the same physical–chemical properties in all organisms.
The approach describes:
• The theory and how to predict the acute toxicity to these organisms;
• Development of an Acute to Chronic ratio [ACR] for only hydrocarbons and for 29 data points.

The logkow used for calculation:
p-xylene= 3.09

Specific details on test material used for the study:

N/A

Details on sampling:

N/A

Details on test solutions:

N/A

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

N/A

Post exposure observation period:

N/A

Hardness:

N/A

Test temperature:

N/A

pH:

N/A

Dissolved oxygen:

N/A

Salinity:

N/A

Conductivity:

N/A

Nominal and measured concentrations:

N/A

Details on test conditions:

N/A

Key result

Duration:

21 d

Dose descriptor:

NOELR

Effect conc.:

1.134 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

not specified

Remarks on result:

ChV (chronic value, QSAR)

Details on results:

N/A

Results with reference substance (positive control):

N/A

Reported statistics and error estimates:

N/A

N/A

Conclusions:

The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 1.134 mg/L. The target substance is a hydrocarbon acting via baseline toxicity, and falls within the parametric, structural and mechanistic domain of the model.

Executive summary:

The long-term aquatic toxicity to this substance was estimated using the Target Lipid Model based on methodologies described by McGrath et al. (2004, 2015). The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 1.134 mg/L.

Reference 5

Endpoint:

long-term toxicity to fish, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

The Target Lipid Model (TLM) is a framework that relates toxicity to the physicochemical properties of a nonpolar organic constituent. It is a well documented and peer reviewed model that is widely used across the petrochemicals industry. This substance fits within the criteria of the model and there are no reservations about the validity of the model runs. It is expected that this data is reliable with restrictions.

Qualifier:

no guideline required

Principles of method if other than guideline:

The endpoint calculated is the LL50, EL50, and NOELR -
The narcosis TLM was developed to predict the toxicity of chemicals to aquatic organisms that act via narcosis. It is based on the hypothesis that target lipid is the site of toxic action within the organism, that octanol is the appropriate surrogate, and that target lipid has the same physical–chemical properties in all organisms.
The approach describes:
• The theory and how to predict the acute toxicity to these organisms;
• Development of an Acute to Chronic ratio [ACR] for only hydrocarbons and for 29 data points.

The logkow used for calculation:
xylene = 3.16

Specific details on test material used for the study:

N/A

Details on sampling:

N/A

Details on test solutions:

N/A

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

N/A

Hardness:

N/A

Test temperature:

N/A

pH:

N/A

Dissolved oxygen:

N/A

Salinity:

N/A

Conductivity:

N/A

Nominal and measured concentrations:

N/A

Details on test conditions:

N/A

Key result

Duration:

21 d

Dose descriptor:

NOELR

Effect conc.:

0.975 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

not specified

Remarks on result:

ChV (chronic value, QSAR)

Details on results:

N/A

Results with reference substance (positive control):

N/A

Reported statistics and error estimates:

N/A

N/A

Conclusions:

The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 0.975 mg/L. The target substance is a hydrocarbon acting via baseline toxicity, and falls within the parametric, structural and mechanistic domain of the model.

Executive summary:

The long-term aquatic toxicity to this substance was estimated using the Target Lipid Model based on methodologies described by Mcgrath et al. (2004). The estimated NOELR for Oncorhynchus mykiss exposed to this substance is 0.975 mg/L.

Description of key information

The effects of p-xylene to the early-life stage of fish (Danio rerio/ zebrafish) were determined according to OECD Guideline 210. An extended limit test was conducted under flow-through conditions with the nominal test item concentrations of 2.50 - 5.00 - 10.0 mg/L, corresponding to arithmetic mean measured test item concentrations of 0.714 – 1.29 – 2.79 mg/L. The NOEC and LOEC were determined to be 0.714 and 1.29 mg/L, respectively, based on post-hatch and overall survival.

The estimated NOELR values from TLM QSAR were 0.894 -1.134 mg/L.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

NOEC

Effect concentration:

0.714 mg/L

Additional information

Noack (2017) measured the effects of p-xylene to the early-life stage of fish (Danio rerio/ zebrafish). The effects were determined according to OECD Guideline 210. An extended limit test was conducted under flow-through conditions with the nominal test item concentrations of 2.50 - 5.00 - 10.0 mg/L, corresponding to arithmetic mean measured test item concentration of 0.714 – 1.29 – 2.79 mg/L. The NOEC and LOEC were determined to be 0.714 and 1.29 mg/L respectively based on post-hatch and overall survival.

 

A TLM modeling framework was used to support values derived experimentally and are presented as supporting studies.

 

 

The estimated NOELR values from TLM QSAR were 0.894 - 1.134 mg/L.